In order to find the optimal heat input for simulating the welding of the coarse-grained heat-affected zone (CGHAZ) of a novel Q690 MPa V-N microalloyed medium and heavy plate, the study investigated the precipitation of V (C, N), microstructural changes, and impact toughness under five different heat inputs (E). The results show that in the CGHAZ, as the heat input increases, the dominant microstructure changes from intragranular acicular ferrite (IGAF) and lath bainitic ferrite (LBF) to polygonal ferrite (PF) and a small amount of IGAF. At the same time, the area fraction of the brittle phase martensite/austenite (M/A) constituents increased from 4.96% to 7.95% as heat input increased, and the microhardness difference between the M/A constituents and the matrix significantly increased. In addition, with the E increases, the fraction of high-angle grain boundaries (HAGBs), which can hinder crack propagation, increases from 59.2% to 62.2% and then decreases from 62.2% to 49.3%. Moreover, the impact toughness of the simulated CGHAZ of the Q690 MPa V-N microalloyed medium and heavy plate first increases from 62 J to 100 J and then decrease to 20 J.